TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22601	68026;68027;68028	chr2:178579229;178579228;178579227	chr2:179443956;179443955;179443954
N2AB	20960	63103;63104;63105	chr2:178579229;178579228;178579227	chr2:179443956;179443955;179443954
N2A	20033	60322;60323;60324	chr2:178579229;178579228;178579227	chr2:179443956;179443955;179443954
N2B	13536	40831;40832;40833	chr2:178579229;178579228;178579227	chr2:179443956;179443955;179443954
Novex-1	13661	41206;41207;41208	chr2:178579229;178579228;178579227	chr2:179443956;179443955;179443954
Novex-2	13728	41407;41408;41409	chr2:178579229;178579228;178579227	chr2:179443956;179443955;179443954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-127
• Domain position: 42
• Structural Position: 127
• Q(SASA): 0.4911
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
S/T	rs1035871236	None	None	N	0.316	0.078	0.229264304666	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/T	rs1035871236	None	None	N	0.316	0.078	0.229264304666	gnomAD-4.0.0	6.5773E-06	None	None	None	None	N	None	2.41418E-05	0	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
S/A	0.1008	likely_benign	0.0935	benign	-0.503	Destabilizing	None	N	0.336	neutral	N	0.464004891	None	None	N
S/C	0.1398	likely_benign	0.1471	benign	-0.28	Destabilizing	0.824	D	0.501	neutral	None	None	None	None	N
S/D	0.5067	ambiguous	0.4585	ambiguous	-0.053	Destabilizing	0.149	N	0.456	neutral	None	None	None	None	N
S/E	0.5959	likely_pathogenic	0.5513	ambiguous	-0.15	Destabilizing	0.149	N	0.422	neutral	None	None	None	None	N
S/F	0.3245	likely_benign	0.2719	benign	-1.161	Destabilizing	0.555	D	0.569	neutral	None	None	None	None	N
S/G	0.1338	likely_benign	0.1241	benign	-0.601	Destabilizing	0.035	N	0.433	neutral	None	None	None	None	N
S/H	0.437	ambiguous	0.4269	ambiguous	-1.224	Destabilizing	0.935	D	0.499	neutral	None	None	None	None	N
S/I	0.2289	likely_benign	0.2036	benign	-0.371	Destabilizing	0.235	N	0.546	neutral	None	None	None	None	N
S/K	0.7465	likely_pathogenic	0.7129	pathogenic	-0.479	Destabilizing	0.149	N	0.424	neutral	None	None	None	None	N
S/L	0.1577	likely_benign	0.1392	benign	-0.371	Destabilizing	0.062	N	0.535	neutral	N	0.518378093	None	None	N
S/M	0.241	likely_benign	0.2218	benign	0.062	Stabilizing	0.555	D	0.501	neutral	None	None	None	None	N
S/N	0.1646	likely_benign	0.1497	benign	-0.219	Destabilizing	0.149	N	0.483	neutral	None	None	None	None	N
S/P	0.6061	likely_pathogenic	0.4802	ambiguous	-0.388	Destabilizing	0.484	N	0.482	neutral	N	0.503179354	None	None	N
S/Q	0.5765	likely_pathogenic	0.5606	ambiguous	-0.533	Destabilizing	0.555	D	0.496	neutral	None	None	None	None	N
S/R	0.7261	likely_pathogenic	0.6945	pathogenic	-0.279	Destabilizing	0.38	N	0.486	neutral	None	None	None	None	N
S/T	0.0765	likely_benign	0.0703	benign	-0.322	Destabilizing	None	N	0.316	neutral	N	0.450595663	None	None	N
S/V	0.2039	likely_benign	0.1914	benign	-0.388	Destabilizing	0.081	N	0.537	neutral	None	None	None	None	N
S/W	0.5226	ambiguous	0.4851	ambiguous	-1.136	Destabilizing	0.935	D	0.636	neutral	None	None	None	None	N
S/Y	0.236	likely_benign	0.2137	benign	-0.863	Destabilizing	0.555	D	0.579	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.